Haemophilus influenzae is an important childhood pathogen. Approximately 10,000 children each year acquire meningitis due to this organism; of these most survive, but with serious neurologic sequelae. Ninety-five percent of invasive H. influenzae disease is due to type b organisms. These are uncommon in surveys of upper respiratory flora, in contrast to the ubiquity of unencapsulated isolates. To better understand the pathogenesis of invasive type b disease we intend to clone the capsulation genome in an avirulent laboratory-maintained strain, Rd. We will use a Haemophilus R-plasmid encoding for ampicillin resistance as the cloning vechile. Once cloned, the gene 1 be mapped and the protein gene products identified. Regulation will be examined and role in virulence assigned by use of an animal model system of infection, and in vitro assays. The cloned gene will also be used as a molecular probe to define the genetic relationship of unencapsulated H. influenzae to type b organisms. Understanding the mechanism of invasive H. influenzae disease, and the genetics and regulation of capsulation of type b organism will allow development of new approaches to control this disease.